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Published on: January 21, 2020
Expression of P2X4 receptor by lesional activated microglia during formalin-induced inflammatory pain
Liang-Hao Guo1, Katrin Trautmann, Hermann J Schluesener
1Institute of Brain Research, University of Tuebingen, Calwer Str.3, D-72076 Tuebingen, Germany. lianghao.guo@uni-tuebingen.de
Abstract:
P2X4 receptor (P2X4R) is an ion channel gated by adenosine 5'-triphosphate. Here we report the presence and the distribution of P2X4R in rat spinal cord by immunohistochemical analysis in an inflammatory pain model. Peripheral inflammation was induced by subcutaneous injection of 4% formalin into the rat hindpaw. Morphology, spatial localization, and activation state of P2X4R+ cells were described at 1, 5, 7, 14, and 28 days after injury. In normal and saline treated control rats, P2X4R was rarely seen. After formalin administration, an increase of P2X4R+ microglia were observed in the spinal cord dorsal horn on the side ipsilateral to the injection, reaching maximal levels by day 7, and then decreasing to normal levels by day 14. This implicates a role of P2X4R in the spinal inflammatory pain process. Furthermore, formalin-induced region-specific increase in activated microglia was confirmed by ED1 and endothelial monocytes activating polypeptide II (EMAP-II) expression. In conclusion, this is the first demonstration that P2X4R is expressed by microglia in the inflammatory pain.
Insights
The P2X4 receptor (P2X4R), an ATP-gated ion channel, is expressed by microglia in the rat spinal cord during inflammatory pain. Its expression increases following formalin injection, peaking at day 7, and then subsides.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- The P2X4 receptor (P2X4R) is an ion channel activated by adenosine 5'-triphosphate.
- Its role in inflammatory pain, particularly in the spinal cord, requires further elucidation.
Purpose of the Study:
- To investigate the presence, distribution, and temporal expression of P2X4R in the rat spinal cord during an inflammatory pain model.
- To determine if P2X4R is expressed by microglia in response to peripheral inflammation.
Main Methods:
- Immunohistochemical analysis was performed on rat spinal cords at multiple time points (1, 5, 7, 14, 28 days) after formalin-induced hindpaw inflammation.
- Expression of P2X4R, ED1, and EMAP-II was assessed to identify microglia and their activation state.
Main Results:
- P2X4R was rarely observed in normal or saline-treated control rats.
- Following formalin injection, P2X4R-positive microglia significantly increased in the spinal cord dorsal horn ipsilateral to the injury.
- P2X4R expression peaked by day 7 and returned to baseline by day 14, correlating with increased activated microglia (ED1 and EMAP-II expression).
Conclusions:
- This study provides the first evidence that P2X4R is expressed by microglia in the context of spinal inflammatory pain.
- P2X4R plays a significant role in the neuroinflammatory processes underlying inflammatory pain in the spinal cord.
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